polyalanine repeat diseases

 Expansions of trinucleotide repeats encoding polyalanine tracts have been recognized as the cause of several diseases, predominantly congenital malformation syndromes.

 In 2005, nine genes with alanine tract expansions have been described.

 With the exception of PABPN1, which codes for a poly(A)-binding protein, all these genes encode transcription factors that play important roles during development.

 Expansions of polyalanine tracts beyond a certain threshold result in protein misfolding, protein aggregation and subsequent protein degradation.

 Polyalanine tracts are relatively common in the genome and occur most frequently in transcription factors and other proteins with nuclear localization.

 The molecular role of alanine tracts is unknown, but their strong evolutionary conservation suggests the existence of potent functional or structural constraints.

Types

FOXL2	blepharophimosis-ptosis-epicanthus inversus syndactyly	BPES	MIM.110100
ZIC2	holoprosencephaly 5	HPE5	MIM.609637
PHOX2B	congenital failure of autonomic control	-	MIM.209880
ARX	X-linked infantile spasm syndrome	-	MIM.308350
SOX3	X-linked mental retardation with isolated growth hormone deficiency	MRGH	MIM.300123
RUNX2	cleidocranial dysplasia	CCD	MIM.119600
HOXA13	hand-foot-genital syndrome	HFGS	MIM.140000
HOXD13	synpolydactyly 1	SPD1	MIM.186000
PABPN1	oculopharyngeal muscular dystrophy	OPMD	MIM.164300

See also

 trinucleotide repeats

References

 Albrecht A, Mundlos S. The other trinucleotide repeat: polyalanine expansion disorders. Curr Opin Genet Dev. 2005 Jun;15(3):285-93. PMID: 15917204

 Amiel J, Trochet D, Clement-Ziza M, Munnich A, Lyonnet S. Polyalanine expansions in human. Hum Mol Genet. 2004 Oct 1;13 Suppl 2:R235-43. PMID: 15358730

 Brown LY, Brown SA. Alanine tracts: the expanding story of human illness and trinucleotide repeats. Trends Genet. 2004 Jan;20(1):51-8. PMID: 14698619